Multi-frequency impedance monitoring system

ABSTRACT

A system and method is provided to measure intrathoracic complex impedance and to identify and indicate disease conditions based on the impedance measurements. Multiple impedance vectors may be taken into account, and an optimal vector may be selected to provide the most useful impedance measurement for the identification and indication of disease conditions.

RELATED APPLICATION

This application is a divisional of U.S. patent application Ser. No.12/112,765, filed Apr. 30, 2008 entitled “MULTI-FREQUENCY IMPEDANCEMONITORING SYSTEM”, herein incorporated by reference in its entirety.

BACKGROUND

The present invention relates to systems and methods for measuringintrathoracic impedance (intracardiac, intravascular, subcutaneous,etc.) in an implantable medical device (IMD) system.

In systems employing IMDs such as pacemakers, defibrillators, andothers, it has proven beneficial to provide the ability to measureintrathoracic impedance. Intrathoracic impedance measuring is performedby monitoring the voltage differential between pairs of spacedelectrodes as current pulses are injected into those same leads or intoother electrodes. Changes in the measured intrathoracic impedance mayindicate certain disease conditions that can be addressed by delivery oftherapy or alarm notification, for example. The efficacy of impedancemonitoring to evaluate and monitor pulmonary edema and worseningcongestive heart failure has been demonstrated in the OptiVol® FluidStatus Monitoring system provided by Medtronic, Inc. of Minneapolis,Minn.

Further improvements in the ability of an intrathoracic impedancemeasuring system to identify and monitor disease conditions would beuseful.

SUMMARY

A system and method is provided to measure intrathoracic impedance andto identify and monitor disease conditions based on the impedancemeasurements. Multiple electrode combinations may be taken into account,and an optimal combination of electrodes may be selected to provide themost useful (e.g., sensitive and specific) impedance measurement for theidentification and monitoring of disease conditions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram depicting the paths taken by low frequency currentand high frequency current injected through a homogenous tissue segment.

FIG. 2 is a diagram illustrating an example of the relative placement ofan IMD and a lead carrying electrodes for performing an intrathoracicimpedance measurement.

FIG. 3 is a graph illustrating the magnitude of the impedance measuredbetween electrodes in a homogenous tissue segment for a low frequencyinjection current and a high frequency injection current.

FIG. 4 is a flow diagram illustrating an example of a method ofmonitoring the difference between impedance magnitudes at low and highinjection current frequencies.

FIG. 5 is a phasor diagram illustrating the real component and thereactive component of impedance measured in response to a low frequencyinjection current in healthy tissue.

FIG. 6 is a phasor diagram illustrating the real component and thereactive component of impedance measured in response to a low frequencyinjection current in diseased tissue such as in pulmonary fluidcongestion.

FIG. 7 is a flow diagram illustrating an example of a method ofmonitoring changes in phase angle and/or impedance magnitude in responseto low frequency injection current in order to detect pulmonary edema.

FIG. 8 is a phasor diagram illustrating the real component and thereactive component of impedance measured in response to a high frequencyinjection current in healthy tissue.

FIG. 9 is a phasor diagram illustrating the real component and thereactive component of impedance measured in response to a high frequencyinjection current in diseased tissue such as myocardial ishemia.

FIG. 10 is a flow diagram illustrating an example of a method ofmonitoring changes in phase angle and/or impedance magnitude in responseto high frequency injection current in order to detect myocardialischemia.

FIGS. 11A-11D are diagrams showing examples of uses of electrodesconfigured as shown in FIG. 2 with a lead extending into the rightventricle (RV) and electrodes carried by the lead positioned in the RV,the right atrium, the superior vena cava and the subclavian vein.

FIG. 12 is a diagram illustrating another example of the relativeplacement of an IMD and a lead carrying electrodes for performing anintrathoracic impedance measurement.

FIGS. 13A-13D are diagrams showing examples of uses of electrodesconfigured as shown in FIG. 12 with a distal end of a lead placed overthe left ventricle (LV) via the cardiac vein, and electrodes carried bythe lead positioned over the LV, in the right atrium, in the subclavianvein, and adjacent to an IMD..

FIG. 14 is a diagram illustrating another example of the relativeplacement of an IMD and a lead carrying electrodes for performing anintrathoracic impedance measurement.

FIGS. 15A-15D are diagrams showing examples of uses of electrodesconfigured as shown in FIG. 14 with a distal end of a lead placed in theinferior vena cava (IFC) and electrodes carried by the lead positionedin the IVC, the right atrium, the superior vena cava and the subclavianvein.

FIG. 16 is a diagram illustrating another example of the relativeplacement of an IMD and a lead carrying electrodes for performing anintrathoracic impedance measurement.

FIGS. 17A, 17B and 17C are diagrams showing examples of uses ofelectrodes configured as shown in FIG. 16 with electrodes carried on theIMD housing implanted subcutaneously in the left lateral superiorthorax, with a distal end of the lead placed over the left ventricle(LV) via the cardiac vein, and with electrodes carried by the leadpositioned over the LV, in the right atrium, and in the subclavian vein.

FIG. 18 is a diagram illustrating an example of a subcutaneous leadconfigured with its distal end placed in the left lateral thorax.

FIGS. 19A and 19B are diagrams showing examples of uses of electrodesconfigured as shown in FIG. 2 in conjunction with the subcutaneous leadconfiguration shown in FIG. 18.

FIGS. 19C and 19D are diagrams showing examples of uses of electrodesconfigured as shown in FIG. 12 in conjunction with the subcutaneous leadconfiguration shown in FIG. 18.

FIG. 20 is a diagram illustrating an example of an impedance waveformcontaining a high frequency cardiac component superimposed on a lowfrequency respiratory component and a DC or mean component.

FIG. 21 is a diagram illustrating a Fast Fourier Transform (FFT)analysis of the impedance waveform shown in FIG. 20.

FIG. 22 is a diagram illustrating an example of an impedance waveformobtained from a transthoracic subcutaneous electrode vectorconfiguration utilizing electrodes positioned substernal and bilateralon the left and right thorax.

FIG. 23 is a diagram illustrating a FFT analysis of the impedancewaveform shown in FIG. 22 where the high frequency cardiac component isattenuated.

FIG. 24 is a diagram illustrating an example of an impedance waveformobtained from a combination subcutaneous and intracardiac electrodevector configuration utilizing electrodes positioned in the rightventricle, the left ventricle, and the device housing.

FIG. 25 is a diagram illustrating a FFT analysis of the impedancewaveform shown in FIG. 24.

FIG. 26 is a diagram illustrating a method of calculating a ratiobetween the cardiac component and the respiratory component of animpedance waveform utilizing a threshold adjustment technique.

FIG. 27 is a flow diagram illustrating a method of detecting the peak ofthe respiratory component of the impedance waveform during endinspiration and of detecting the peak impedance of the cardiac componentof the impedance waveform during end expiration.

DETAILED DESCRIPTION

FIG. 1 is a diagram depicting path 20 taken by low frequency currentinjected through a selected tissue segment T, and path 22 taken by highfrequency current injected through tissue segment T. Low frequencycurrent flows primarily in path 20 through extracellular spaces intissue segment T, due to the frequency dependent resistance provided bythe cellular membrane of cells C. By contrast, high frequency currentreduces the capacitive reactance component of the cellular membrane ofcells C, allowing current to flow more uniformly through tissue segmentT. This difference in the response of tissue segment T to currents ofdifferent frequencies can be utilized to identify and predict diseaseconditions, examples of which are discussed in detail below.

FIG. 2 is a diagram illustrating an example of the relative placement ofIMD 30 and lead 32 carrying electrodes 34 for performing anintrathoracic impedance measurement. IMD 30 is implantable under theskin of a patient in the chest area, and includes impedance measurementcircuitry and processing circuitry, as well as various leads for sensingand therapy delivery functions. In FIG. 2, for example, lead 32 is shownextending into the right ventricle (RV), with electrodes 34 positionedin the RV, the right atrium, the superior vena cava and the subclavianvein. By injecting a current between selected electrodes 34, a voltagedifferential between those electrodes can be created that allows theimpedance of the tissue between the electrodes to be measured. Manyother configurations and arrangements of electrodes 34, leads 32, andIMD 30 are possible, and other examples are discussed in a later sectionbelow.

Measurement of Impedance Magnitude Differences at low and HighFrequencies

FIG. 3 is a graph illustrating the magnitude of the impedance measuredbetween electrodes in a tissue segment (such as between selectedelectrodes 34 shown in FIG. 2) for a low frequency injection current(curve 40) and a high frequency injection current (curve 42). Asdiscussed above with respect to FIG. 1, low frequency current flowsprimarily through extracellular spaces in tissue, while high frequencycurrent reduces the capacitive reactance component of the cellularmembranes, allowing current to flow more uniformly through the tissue.Thus, the impedance measured in response to the low frequency injectioncurrent is larger than the impedance measured in response to the highfrequency injection current. Moreover, the difference 44 between the lowfrequency impedance and the high frequency impedance of the tissue isindicative of the state of the tissue. Specifically, the progression ofpulmonary edema causes the difference between the low frequencyimpedance magnitude and the high frequency impedance magnitude todecrease, due to the accumulation of fluid in the extracellular spaces.Thus, measurement of the magnitudes of impedance in response to a lowfrequency injection current and to a high frequency injection current,and calculating the difference between the impedance magnitudes, canproduce an indicator of disease such as heart failure, pulmonary edema,or others.

FIG. 4 is a flow diagram illustrating an example of a method ofmonitoring the difference between impedance magnitudes at low and highinjection current frequencies. After an electrode vector configurationis selected (step 50), a low frequency current is injected into anelectrode pair (step 51), and the magnitude of the impedance (Z_(L)) atlow frequency is measured (step 52). Then, a high frequency current isinjected into the electrode pair (step 54), and the magnitude of theimpedance (Z_(H)) at high frequency is measured (step 56). The lowfrequency impedance (Z_(L)) is then compared to the high frequencyimpedance (Z_(H)) (step 58). If the low frequency impedance (Z_(L)) issignificantly greater than the high frequency impedance (Z_(H)), thenconditions are normal and there is no indication of heart failure orpulmonary edema (step 60). However, if the low frequency impedance(Z_(L)) is not significantly greater than the high frequency impedance(Z_(H)), then the difference between the low frequency impedance (Z_(L))and the high frequency impedance (Z_(H)) is evaluated to determine thestate of the tissue (step 62). From this evaluation, the onset andprogression of disease such as heart failure or pulmonary edema isindicated (step 64). For example, a smaller difference between the lowfrequency impedance (Z_(L)) and the high frequency impedance (Z_(H)) mayindicate a more advanced progression of heart failure or, morespecifically, pulmonary edema.

In an exemplary embodiment, with respect to the injection currentsdescribed above, the low frequency is no greater than about 10kiloHertz, and the high frequency is about ten times greater than thelow frequency, such as between about 50 kiloHertz and 100 kiloHertz.

Measurement of Real and Reactive Components of Impedance at lowFrequency

FIGS. 5 and 6 are exemplary phasor diagrams illustrating the realcomponent (R) and the reactive component (X_(C)) of impedance (Z),measured in response to a low frequency injection current in healthytissue (FIG. 5) and in diseased tissue having fluid accumulated inextracellular spaces (FIG. 6). The impedance (Z) is calculated accordingto the following formula:

Z=√(R ² +X _(c) ²)  (Eq. 1).

The corresponding phase angle (θ) of the impedance phasor is calculatedaccording to the following formula:

θ=tan⁻¹ (X _(c) /R)

As can be seen from the examples in FIGS. 5 and 6, the accumulation offluid in extracellular spaces results in an increase in the phase angle(θ) of the impedance phasor (such as from 45° for healthy tissue inFIGS. 5 to 60° for diseased tissue in the example of FIG. 6), and alsoin a decrease in the total magnitude of impedance (Z), due to a decreasein the real component (R) of impedance caused by a decrease in theextracellular volumes of the cells, which causes the cells'extracellular resistance to decrease. The increase in phase angle or thedecrease in impedance magnitude (or both) is detectable as an indicationof the onset or progression of cardiopulmonary disease such as pulmonaryedema secondary to heart failure.

FIG. 7 is a flow diagram illustrating an example of a method ofmonitoring changes in phase angle and/or impedance magnitude in responseto low frequency injection current in order to detect pulmonary edema.After an electrode vector configuration is selected (step 70), a lowfrequency current is injected into an electrode pair (step 71), and themagnitude and phase angle of the impedance is measured (step 72). Themagnitude of the impedance is then compared to a reference value (step74), and it is determined whether the magnitude of the impedance hasdecreased from the reference value (step 76). If the impedance hasdecreased from the reference value, the onset/progression of pulmonaryedema and the like is indicated (step 78).

The next step is to compare the phase angle of the impedance to areference value (step 80), and to determine whether the phase angle hasincreased from the reference value (step 82), which would indicate thatthe real component of the impedance has decreased in comparison to thereactive component of the impedance (see FIGS. 5 and 6). If the phaseangle of the impedance has not increased from the reference value, thereis no indication of pulmonary edema (step 84). If the phase angle of theimpedance has increased from the reference value, the onset/progressionof pulmonary edema is indicated (step 86).

A method according to FIG. 7 shows separate determinations of theonset/progression of pulmonary edema based on the magnitude and thephase angle of impedance. In some embodiments, a determination of eithera decreased magnitude of impedance or an increased phase angle ofimpedance will result in an indication of the onset/progression ofpulmonary edema. In other embodiments, both a decrease in the magnitudeof impedance and an increase in the phase angle of impedance arerequired to indicate the onset/progression of pulmonary edema. In stillfurther embodiments, separate indications of the onset/progression ofpulmonary edema based on a relative change in the magnitude of impedanceand the phase angle of impedance are provided.

Measurement of Real and Reactive Components of Impedance at HighFrequency

FIGS. 8 and 9 are phasor diagrams illustrating the real component (R)and the reactive component (X_(C)) of impedance (Z), measured inresponse to a high frequency injection current in healthy tissue (FIG.8) and in diseased tissue such as in myocardial ischemia (FIG. 9). Theimpedance (Z) and phase angle (θ) are calculated according to Eq. 1 andEq. 2 above, respectively. As can be seen from the examples shown inFIGS. 8 and 9, ischemia in the tissue results in a decrease in the phaseangle (θ) of the impedance phasor (such as from 45° for healthy tissuein

FIGS. 8 to 35° for ischemic tissue in FIG. 9), and also in an increasein the total magnitude of impedance (Z), due to an increase in theresistive component (R) of impedance caused by decreased extracellularvolume. The decrease in phase angle or the increase in impedancemagnitude (or both) is detectable as a potential indicator of myocardialischemia.

Over time, the cells in ischemic tissue will rupture, so thatintracellular and extracellular fluid drains out the lymphatic system.This causes the real component (R) of impedance to increase due to thedecreased volume of the cell, and also causes the reactive component(X_(C)) of impedance to increase due to the decreased surface area ofthe cell. As a result, the total magnitude of impedance increasessignificantly, which is detectable as a potential indicator ofmyocardial necrosis or myocardial infarct.

FIG. 10 is a flow diagram illustrating an example of a method ofmonitoring changes in phase angle and/or impedance magnitude in responseto high frequency injection current in order to detect disease such asmyocardial ischemia. After an electrode vector configuration is selected(step 90), a high frequency current is injected into an electrode pair(step 91), and the magnitude and phase angle of the impedance ismeasured (step 92). The magnitude of the impedance is then compared to areference value (step 94), and it is determined whether the magnitude ofthe impedance has increased from the reference value (step 96). If theimpedance has increased from the reference value, an indication oftissue ischemia is made (step 98).

The next step is to compare the phase angle of the impedance to areference value (step 100), and to determine whether the phase angle hasdecreased from the reference value (step 102), which would indicate thatthe resistive component of the impedance has increased in comparison tothe reactive component of the impedance (see FIGS. 8 and 9). If thephase angle of the impedance has not decreased from the reference value,there is no indication of tissue ischemia (step 104). If the phase angleof the impedance has decreased from the reference value, an indicationof tissue ischemia is made (step 106).

A method according to FIG. 10 shows separate determinations of tissueischemia based on the magnitude and the phase angle of impedance. Insome embodiments, a determination of either an increased magnitude ofimpedance or a decreased phase angle of impedance will result in anindication of tissue ischemia. In other embodiments, both an increase inthe magnitude of impedance and a decrease in the phase angle ofimpedance are required to indicate tissue ischemia. In still furtherembodiments, separate indications of tissue ischemia based on a relativechange in the magnitude of impedance and the phase angle of impedanceare provided.

Electrode Placement and Vector Selection

As discussed above, FIG. 2 illustrates an example of the relativeplacement of IMD 30 and lead 32 carrying electrodes 34 for performing anintrathoracic impedance measurement, with lead 32 extending into theright ventricle (RV), and electrodes 34 positioned in the RV, the rightatrium, the superior vena cava and the subclavian vein. FIGS. 11A-11Dshow examples of how electrodes 34 may be used in this configuration.FIG. 11A illustrates a scenario in which a stimulation vector (S) isestablished between an electrode in the right atrium (RA) and anelectrode in the RV, so that transvalvular impedance can be measured byvoltage sense vectors (VS). FIG. 11B illustrates a scenario in which astimulation vector (S) is established between an electrode adjacent toIMD 30 and an electrode in the RV, so that left heart impedance can bemeasured by voltage sense vectors (VS). FIG. 11C illustrates a scenarioin which a stimulation vector (S) is established between an electrode inthe superior vena cava and an electrode in the RV, so that right heartimpedance can be measured by a voltage sense vector (VS). FIG. 11Dillustrates a scenario in which a stimulation vector (S) is establishedbetween an electrode adjacent to IMD 30 and an electrode in the superiorvena cava, so that superior lung impedance can be measured by a voltagesense vector (VS).

FIG. 12 illustrates another example of the relative placement of IMD 30and lead 32 carrying electrodes 34 for performing an intrathoracicimpedance measurement, with the distal end of lead 32 placed over theleft ventricle (LV) via the cardiac vein, and electrodes 34 positionedover the LV, in the right atrium, and in the subclavian vein. FIGS.13A-13D show examples of how electrodes 34 may be used in thisconfiguration. FIG. 13A illustrates a scenario in which a stimulationvector (S) is established between two electrodes spanning the LV, sothat LV impedance can be measured by voltage sense vectors (VS). FIG.13B illustrates a scenario in which a stimulation vector (S) isestablished between a distal electrode adjacent the LV and an electrodein the right atrium (RA), so that right atrial impedance can be measuredby voltage sense vectors (VS). FIG. 13C illustrates a scenario in whicha stimulation vector (S) is established between a distal electrodeadjacent the LV and an electrode adjacent IMD 30, so that left lungimpedance can be measured by voltage sense vectors (VS). FIG. 13Dillustrates a scenario in which a stimulation vector (S) is establishedbetween an electrode in the RA and an electrode adjacent IMD 30, so thatsuperior left lung impedance can be measured by voltage sense vectors(VS). Lead 32 may alternatively be positioned to provide electrodes 34epicardially over the LV to allow similar measurements.

FIG. 14 illustrates another example of the relative placement of IMD 30and lead 32 carrying electrodes 34 for performing an intrathoracicimpedance measurement, with the distal end of lead 32 placed in theinferior vena cava (IVC), and electrodes 34 positioned in the IVC, rightatrium, superior vena cava and subclavian vein. FIGS. 15A-15D showexamples of how electrodes 34 may be used in this configuration. FIG.15A illustrates a scenario in which a stimulation vector (S) isestablished between two electrodes spanning the IVC, so that IVCimpedance can be measured by a voltage sense vector (VS). FIG. 15Billustrates a scenario in which a stimulation vector (S) is establishedbetween an electrode in the RA and an electrode in the superior venacava, so that superior vena cava impedance can be measured by a voltagesense vector (VS). FIG. 15C illustrates a scenario in which astimulation vector (S) is established between an electrode in the IVCand an electrode in the superior vena cava, so that central venousimpedance can be measured by a voltage sense vector (VS). FIG. 15Dillustrates a scenario in which a stimulation vector (S) is establishedbetween an electrode in the IVC and an electrode in adjacent to IMD 30,so that atrial impedance can be measured by a voltage sensor vector(VS).

FIG. 16 illustrates another example of the relative placement of IMD 30carrying electrodes 34 and lead 32 carrying electrodes 34 for performingan intrathoracic impedance measurement, with electrodes 34 carried bythe housing (or “can”) of IMD 30 implanted subcutaneously in the leftlateral superior thorax, with a distal end of lead 32 placed over theleft ventricle (LV) via the cardiac vein, and with electrodes 34 carriedby lead 32 positioned over the LV, in the right atrium (RA), and in thesubclavian vein. FIGS. 17A-17C show examples of how electrodes 34 maybeused in this configuration. FIG. 17A illustrates a scenario in which astimulation vector (S) is established between an electrode in the RA andan electrode carried by the housing of IMD 30, so that upper lungimpedance or RA function can be measured by voltage sense vectors (VS).FIG. 17B illustrates a scenario in which a stimulation vector (S) isestablished between an electrode in the posterior coronary sinus orapplicable cardiac vein and an electrode carried by the housing of IMD30, so that middle lung impedance can be measured by voltage sensevectors (VS).

FIG. 17C illustrates a scenario in which a stimulation vector (S) isestablished between a distal electrode in the subclavian vein adjacentthe LV and an electrode carried by the housing of IMD 30, so that lowerlung impedance can be measured by voltage sense vectors (VS).

FIG. 18 illustrates an example of subcutaneous lead 112 configured withits distal end (carrying electrodes 114) placed in the left lateralthorax. When lead 112 is used in conjunction with intrathoracic lead 32and electrodes 34, left heart and left lung zones can be isolated forimpedance measurements. FIGS. 19A and 19B show examples of howelectrodes 34 and 114 may be used in this configuration, where lead 32and electrodes 34 are arranged as shown in FIG. 2. FIG. 19A illustratesa scenario in which a stimulation vector (S) is established between anelectrode in the RV and the distal electrode in the left lateral thorax,so that left heart and inferior left lung impedance can be measured byvoltage sense vectors (VS). FIG. 19B illustrates a scenario in which astimulation vector (S) is established between an electrode in thesuperior vena cava and the distal electrode in the left lateral thorax,so that left lung impedance can be measured by voltage sense vectors(VS). FIGS. 19C and 19D show examples of how electrodes 34 and 114 maybe used where lead 32 and electrodes 34 are arranged as shown in FIG.12. FIG. 19C illustrates a scenario in which a stimulation vector (S) isestablished between an electrode adjacent the LV and the distalelectrode in the left lateral thorax, so that lower left lung impedancecan be measured by a voltage sense vector (VS). FIG. 19D illustrates ascenario in which a stimulation vector (S) is established between anelectrode in the upper left lung and the distal electrode in the leftlateral thorax, so that upper left lung impedance can be measured by avoltage sense vector (VS).

With this arrangement and the scenarios shown in FIGS. 19C and 19D, thevector configuration shown in FIG. 19D (measuring upper left lungimpedance) can be used as a reference vector for comparison with thevector configuration shown in FIG. 19C (measuring lower left lungimpedance), and the ratio of the two impedance vectors can be used as anindex of the progression of fluid accumulation in zones of the leftlung.

Vector Selection Based on Cardiac and Respiratory Components of Waveform

The impedance waveforms measured via the electrode configurationsdiscussed above contain a high frequency cardiac component superimposedon a low frequency respiratory component and a calculated DC or meancomponent. FIG. 20 is a diagram illustrating an example of such animpedance waveform. Each of the components of the impedance waveform haspotential clinical diagnostic utility (for example, diagnostics fordetecting various conditions are discussed above). The relativemagnitude of each component of the impedance waveform depends on thegeometric electrode configuration. In order to select a particularlyuseful electrode vector from a group of vectors, the ratio of themagnitude of the cardiac impedance component to the magnitude of therespiratory impedance component (CC/RC) is analyzed for each vector, andthe vector having the highest CC/RC ratio is selected as the most usefulfor analysis of the impedance waveform for the selected tissue segment.

Geometric vector configurations may be selected to identify the mostuseful electrode vector for diagnostic monitoring of the lung for fluidaccumulation and respiration, the myocardium for ischemia, or thecardiac chambers for contractility, stroke volume, dilation, orarrhythmia identification. The measurement of impedances in theseregions is useful to measure fluid compartmentalization shifts inpatients with congestive heart failure or pulmonary edema, or to isolatea specific section of the myocardium to detect ischemia, for example. Adetailed discussion of analyzing the morphology of various components ofcomplex impedance waveforms to determine changes in physiologicparameters that may indicate the onset or progression of variousclinical conditions may be found in U.S. Application No. 12/112,655filed on even date herewith, for “System And Method Of DetectingPhysiologic Parameters Based On Complex Impedance Waveform Morphology”by T. Zielinski, D. Hettrick and E. Warman (Attorney Docket No.M933.12-0117 (P26629.00).

The impedance waveform shown in FIG. 20 may be obtained from asubcutaneous, intracardiac, or combination thereof electrode vectorconfiguration. Two positive pressure ventilation (PPV) respiratorycycles are shown. Parameters illustrated in FIG. 20 include arespiratory cycle (RC) time, an end expiratory impedance component(EEIC) time, and an inspiratory impedance component (labeled as PPV).Cardiac impedance components appear as high frequency components of thewaveform.

FIG. 21 is a diagram illustrating a Fast Fourier Transform (FFT)analysis of the impedance waveform shown in FIG. 20. As shown in thediagram, the high frequency cardiac component (CC) of the impedancewaveform is easily visible and separated from the low frequencyrespiratory component (RC) of the impedance waveform. A FFT analysis isone example of a method that can be used to calculate the ratio of themagnitude of the high frequency CC of impedance to the low frequency RCof impedance, to identify an electrode vector having the highest CC/RCratio for selection to analyze and identify certain physiologicalconditions and disease states.

FIG. 22 is a diagram illustrating an example of an impedance waveformobtained from a transthoracic subcutaneous electrode vectorconfiguration utilizing electrodes positioned substernal and bilateralon the left and right thorax. As can be seen in FIG. 22, the impedancewaveform has a highly attenuated high frequency cardiac component (CC),such that only the low frequency respiratory component (RC) of theimpedance waveform is even observable. FIG. 23 is a diagram illustratinga Fast Fourier Transform (FFT) analysis of the impedance waveform shownin FIG. 22. As shown in the diagram, the high frequency CC of theimpedance waveform is attenuated and not observable, while the lowfrequency RC of the impedance waveform is easily observable. Thus, theCC/RC ratio in this scenario is low, and this electrode vector wouldtypically not be selected for analysis in order to determinephysiological conditions and disease states.

FIG. 24 is a diagram illustrating an example of an impedance waveformobtained from a combination subcutaneous and intracardiac electrodevector configuration utilizing electrodes positioned in the rightventricle, the left ventricle, and the device housing. As can be seen inFIG. 24, the impedance waveform has a significant, observable highfrequency cardiac component (CC), and a relatively small low frequencyrespiratory component (RC) of the impedance waveform is observable. FIG.25 is a diagram illustrating a Fast Fourier Transform (FFT) analysis ofthe impedance waveform shown in FIG. 24. As shown in the diagram, thehigh frequency CC of the impedance waveform is significant and easilyobservable, separated from the relatively small low frequency RC of theimpedance waveform. Thus, the CC/RC ratio in this scenario is high, andthis electrode vector would highly likely to be selected for analysis inorder to determine physiological conditions and disease states.

FIG. 26 is a diagram illustrating a method of calculating a CC/RC ratioof an impedance waveform utilizing a threshold adjustment technique. Thepeak impedance of the RC of the impedance waveform is detected andmeasured during end inspiration, and the peak impedance of the CC of theimpedance waveform is detected and measured during end expiration. Thismethod is performed as shown in the flowchart of FIG. 27. First, themean of the impedance waveform is detected over a programmable timeperiod, such as fifteen seconds in one embodiment (step 120). Thedetected mean is then set as a first threshold (Z_(A), see FIG. 26; step122). A peak detection algorithm, as is generally known in the art, thendetermines the frequency of the peak impedances (step 124) andidentifies whether the determined frequency is within the limits ofnormal breathing rates (such as below 40 breaths per minute in oneexample; step 126). The peak impedance of the RC is then recorded(Z_(RC), see FIG. 26; step 128). Once this peak is determined, the meanimpedance is divided by two (Z₁₁₂, see FIG. 26; step 130). Then the peakdetection algorithm is again performed to determine the frequency of thepeak impedances below Z₁₁₂ (step 132). The algorithm identifies whetherthe determined frequency is within the limits of normal cardiac rates(such as above 50 beats per minute in one example; step 134), and if itis not, the threshold is again divided by two (step 136) and the processis repeated. Once a valid frequency is determined, the peak impedance ofthe CC (Z_(CC)) is recorded (step 138). These impedance magnitudes foreach vector are then used to determine the optimal electrode vectorconfiguration based on the Z_(CC)/Z_(RC) ratio of each vector (step140).

The system(s) and method(s) described above provide an improved abilityto measure complex intrathoracic impedance and to identify and predictdisease conditions based on the impedance measurements. Multipleimpedance vectors may be taken into account, and an optimal vector maybe selected to provide the most useful impedance measurement for theidentification and prediction of disease conditions.

Although the present invention has been described with reference topreferred embodiments, workers skilled in the art will recognize thatchanges may be made in form and detail without departing from the spiritand scope of the invention.

1. A system for measuring intrathoracic impedance across a plurality ofselected tissue segments, comprising: at least one lead carrying aplurality of electrodes, the electrodes being positioned so thatselected pairs of electrodes span selected ones of the plurality ofselected tissue segments; impedance measurement circuitry for measuringan impedance between the selected pairs of electrodes; and processingcircuitry for evaluating the measured impedance between at least one ofthe selected pairs of electrodes to determine whether the tissue segmentis in a diseased condition, and for providing an indicator of diseasebased on the determination of whether the tissue segment is in adiseased condition.
 2. A system according to claim 1, wherein the atleast one lead is connected to an implantable medical device (IMD) thathouses the impedance measurement circuitry and the processing circuitry.3. A system according to claim 2, wherein the IMD comprises at least oneelectrode.
 4. A system according to claim 3, wherein at least a portionof the at least one lead is positioned over a left ventricle via acardiac vein or epicardially, and the electrodes carried by the at leastone lead are positioned in at least one of the cardiac vein over theleft ventricle, epicardially over the left ventricle, a right atrium,and a subclavian vein.
 5. A system according to claim 1, wherein atleast a portion of the at least one lead is positioned in a rightventricle and the electrodes carried by the at least one lead arepositioned in at least one of the right ventricle, a right atrium, asuperior vena cava and a subclavian vein.
 6. A system according to claim1, wherein at least a portion of the at least one lead is positionedover a left ventricle via a cardiac vein, and the electrodes carried bythe at least one lead are positioned in at least one of the cardiac veinover the left ventricle, a right atrium, and a subclavian vein.
 7. Asystem according to claim 1, wherein at least a portion of the at leastone lead is positioned in an inferior vena cava, and the electrodescarried by the at least one lead are positioned in at least one of theinferior vena cava, a right atrium, a superior vena cava and asubclavian vein.
 8. A system according to claim 1, wherein the at leastone lead includes a first lead positioned in a left lateral thorax, andelectrodes carried by the first lead are positioned in the left lateralthorax.
 9. A system according to claim 8, wherein the at least one leadfurther includes a second lead at least partially positioned in a rightventricle, and electrodes carried by the second lead are positioned inat least one of the right ventricle, a right atrium, a superior venacava and a subclavian vein.
 10. A system according to claim 8, whereinthe at least one lead further includes a second lead at least partiallypositioned over a left ventricle via a cardiac vein, and electrodescarried by the second lead are positioned in at least one of the cardiacvein over the left ventricle, epicardially over the left ventricle, aright atrium, and a subclavian vein.
 11. A system according to claim 1,wherein a pair of the selected pairs of electrodes is selected formeasurement of impedance therebetween based on a determination that aratio between a cardiac component of impedance and a respiratorycomponent of impedance is greatest among the selected pairs ofelectrodes.